Tutor: Ian Dirk Fichtner

Supervisor: Frau Dr. Maria Dinkelacker

Introduction

The immune system is responsible for recognising and eliminating threatening pathogens, such as bacteria, viruses or fungi, however, distinguishing these from endogenous cells and not harming them. CD8+ T cells (CD8s), also referred to as cytotoxic T cells precisely recognise antigens via specific T cell receptors (TCRs). Thus, playing a vital role in this process. In order to prevent an autoreactive self-antigen-CD8 complex that would be harmful to the organism, T cells undergo negative selection in addition to positive selection, in the thymus. This negative selection process is mediated by medullary thymic epithelial cells that are presented to developing T cells, leading to the elimination of binding T cells (mTECs)[@Kyewski]. Auto-antigens fall in two categories: housekeeping antigens (HAs) and tissue restricted antigens (TRAs). While HAs are expressed in a multitude of tissues, TRAs are found to be expressed rather uniquely. This results in HAs experiencing only insignificant amounts of epigenetic inactivation. TRAs in contrast, display silencing extensively in a majority of tissues. To classify as a TRA, an antigen is required to exceed five times the median gene expression within one to four tissue expression profiles [@dinkelacker2019]. An unpublished dataset by Dr. Maria Dinkelacker will be utilised to analyse embryonic development. Antigen expression levels constantly vary during embryogenesis, since different stem cells undergo differentiation. This includes TRA expression levels that display a temporal connection to the development of specific organs. QUELLE Due to this connection they offer an interesting approach to study organ development. Despite spatiotemporally mapping of organogenesis in mice recently, specific timing and expression levels of TRAs remain underexplored. Hence, this project aims to investigate TRA expression profiles within mice over a course of mid- to late embryogenesis. Data by @irie2011 supported this undertaking. This project aims to utilise the datasets on time-dependent embryonic transcriptomes and TRAs to catalogue established TRAs in respect to specific stages of embryonic development to offer a base of data that may support further studies in tissue development.

Figure 1.1: Single chip control (a) The second chip of day E8.5 shows no salience. (b) The first chip of day E12.5 is noticeably lighter in intensity in comparison to other chips.Figure 1.1: Single chip control (a) The second chip of day E8.5 shows no salience. (b) The first chip of day E12.5 is noticeably lighter in intensity in comparison to other chips.

Figure 1.1: Single chip control (a) The second chip of day E8.5 shows no salience. (b) The first chip of day E12.5 is noticeably lighter in intensity in comparison to other chips.